The object of this invention is a suction device, such as a mechanical or electronic pipette comprising a body and an associated end part with an open distal end directed away from the body for removably attaching a tip enclosing a sample space for receiving a liquid sample, the end part enclosing a cylinder space containing a reciprocatingly movable means for receiving a sample to the tip and removing it therefrom.
The object of this invention is also a method for dispensing, transferring, diluting, titrating and/or mixing a liquid with a suction device having an end part enclosing a cylindrical space containing a reciprocatingly moving means for sample taking and removal.
Over approximately the past three decades pipettes have been in use having attached liquid reservoirs, that is pipette tips, from which liquid has escaped to the inner parts of the pipette, for example due to careless operation of the pipette, or in the form of liquid molecules vaporized from the liquid. The contamination of the inner parts of the pipette has jeopardized labour safety and reduced or even completely terminated the reliable operation of the pipette itself. Naturally this cannot be accepted in precise laboratory work.
Due to these problems pipette manufacturers recommend that the pipettes are disassembled and cleaned at regular intervals by the pipette users. In this procedure almost always also the plunger and the gasket of the pipette are re-lubricated and often also the pipette has to be re-calibrated, i.e. the pipetted, dispensed etc. liquid volumes are set to correspond to the volumes set on the scale of the pipette. This disassembling and reassembling of the pipette, in addition to being an inconvenient and laborious procedure, does not guarantee that the pipette would not contain infection agents or other contamination such as DNA- and RNase-contamination which interferes with PCR-work. Therefore some pipette manufacturers have started to manufacture pipettes, which are claimed to be sterilizable in an autoclave. Sterilization in the autoclave docs not, however, remove DNA- and RNase-contamination from the pipette parts. It is a very tedious operation and often the operation itself damages parts of the pipette to such an extent that the pipette will not function sufficiently accurately and reliably any more. When the pipette is used after the sterilization, it is possible that it will be contaminated already with the first pipetting.
U.S. Pat. No. 5,406,856 discloses a suction device which is meant to be used with such disposable tips, which have a tip portion to be inserted into a liquid, the tip portion having an opening for taking a liquid sample and removing it and in which disposable tips that part to be adapted onto the end of the body of the suction device is closed towards the suction device. The form of this closed part and simultaneously its volume can be changed with a means within the end part of the body of the suction device. In this solution the contamination can be prevented, but the disposable tip used is a special tip. In addition it must be noticed, that this special tip is adapted into the ond part of the body of the suction device, whereby the end part must be made greater in its outer dimension than the disposable tip itself.
U.S. Pat. No. 4,444,062 discloses a multichannel suction device having a flexible membrane mounted between the body of the suction device and an attached tipstand so, that rods in the plunger movable within the body of the suction device come into contact with the membrane, when the plunger is pushed down-wards. In this solution the membrane is secured either on the undersurface of the body or on the upper surface of the tipstand or two membranes are used of which the first one is secured on the undersurface of the body and the second one on the upper surface of the tipstand. The tipstand itself is mounted to the body with a screw connection. In an embodiment of this invention, the tipstand assembly consisting of a tipstand with attached tubes and tips attached to these and a membrane secured onto the upper surface of the tipstand can be one disposable moulded plastic unit which is mounted to the body of the suction device with a suitable quick connection method. In the solution according to this patent, nothing is disclosed of the removal of the membrane secured on the undersurface of the tipstand or on the upper surface of the body or on the release of the entire tipstand assembly from the body of the suction device by means of the movement of the plunger.
U.S. Pat. No. 4,296,071 discloses a flexible bellows-like means mounted within the body of the pipette. One end of this bellows-like means is attached fixedly in the body of the pipette and the bellows-like means is not meant to be releasable in accordance with the invention.
The drawbacks mentioned above are avoided with the solution according to the invention. It is characterising to the method according to the invention that the means, such as a plunger, moving reciprocatingly in the cylindrical space enclosed by the end part of the suction device, is brought to move in the direction of the distal end of the end part into contact with a flexible, liquid and gas impermeable membrane of a membrane means, which is mounted in a gas tight manner in the air space formed jointly by the said cylindrical space and the sample space of a tip mounted onto the end part for changing, as a result of deformation of the membrane the volume of the space delimited by the said membrane from the said air space in the direction of that end of the tip, which is to be inserted into the liquid, for taking a sample into the sample space and/or removing it therefrom.
According to a preferred embodiment of the disclosed invention the membrane means in the cylindrical space or mounted in the end part of the suction device can be removed by continuing the movement of the plunger, moving within the cylindrical space, past the positions used in taking and/or removing samples. In another preferred embodiment both the membrane means and the tip can be removed with the movement of the said plunger.
The suction device itself can be as such of a known type operated manually or e.g. electrical, and it can be independently operated or functioning as a part of some apparatus, e.g. a pipette. When in the following description the word xe2x80x98pipettexe2x80x99 is used, it means generally all types of suction devices defined above, which function as pipettes, dispensers, diluters, titraters or mixers or in addition as combinations of all of these or some of them.
It is characterising to the device according to the invention that the suction device contains in its end part a removable membrane means which is mounted in a gas tight manner in the air space jointly defined by the cylindrical space and the sample space of a tip to be attached to the end part and comprising a membrane made of a liquid and gas impermeable, flexible, reversibly deformable material, with which membrane the means movable in the cylindrical space can be brought into contact.
The means, a plunger, reciprocatingly moving in the cylindrical space can thus be brought into contact with the membrane of the said membrane means and the plunger moving further towards the opening in the end part of the suction device brings about a deformation of this membrane, whereby the volume of the space, delimited by the membrane from the said joint air space in the direction of the end of the tip to be inserted in a liquid, changes. When taking samples and/or removing them the movement of the plunger is restricted so that the limit of reversible deformation of the said membrane is not exceeded. During the return movement of the plunger the membrane returns towards its original form and regains it, when the plunger and the membrane disengage. In a preferable embodiment of the suction device, the membrane means is easily attachable and releasable and can advantageously be disposable.
In a preferable embodiment of the invention, the said membrane means is mounted in the cylindrical space in the end part of the suction device preferably to seal against a shoulder in the cylindrical space.
In another preferable embodiment of the suction device according to the invention the said membrane means is mounted in the opening in the distal end of the end part of the suction device, the opening forming a gas passage between the cylindrical space and the sample space of the tip, to seal this opening in a gas tight manner. The plunger, moving reciprocatingly in the cylindrical space, when extending through the opening comes into contact with the said membrane and the plunger moving further into the sample space of the tip brings about a deformation of this membrane, whereby the volume of the sample space of the tip changes, as explained above.
According to the invention the membrane means is preferably mounted in the air space jointly formed by the cylindrical space within the distal end of the end part of the suction device and the sample space of the tip so that the said membrane means extends into the sample space of the tip in a gas-sealing engagement with the inner surface of the sample space of the tip so that the said plunger, when moving within the cylindrical space and preferably extending through the opening in the end part of the suction device, comes into contact with the said membrane of this membrane means and brings about a change in the volume delimited by the membrane from the sample space of the tip for taking a sample and/or removing it therefrom.
In a preferable embodiment of the invention the membrane of the said membrane means is secured to a frame, which is provided with sealingly attachable means for attaching to the opening in the distal end of the end part of the suction device. The membrane frame can be suitably supported against a shoulder formed on the inner surface of the opening and the membrane is preferably mounted to that part of the frame, which extends away from the end part of the suction device. The attachment of the membrane means can also be made with a friction joint to the opening in the distal end of the end part.
The membrane means, especially the mombrane frame, can also ba mounted To the end part e.g. with a snap-fit joint e.g. on the outer surface of the distal end of the end part so, that the membrane covers the opening of the end part. The membrane frame can also be supported by a shoulder formed e.g. in the vicinity of the distal end of the end part, preferably on its outer surface. In a preferable embodiment of the invention, be the frame to be attached to the end part can also provided with means to bring about gas tightness between the said membrane frame and the inner surface of the sample space of the tip to be attached onto the distal end of the end part of the suction device.
According to one embodiment, the membrane means can be a bag-like mean, which is compressible like a bellows, and is mounted in the cylindrical space of the end part of the suction device so that the open mouth of this bag-like means attaches, forming a gas-tight seal, to the distal end of the end part of the suction device. This bellows-like membrane means is preferably made of such air and liquid impermeable, flexible material, that the compressing force exerted by the plunger moving in the cylindrical space to the closed end of the bellows-like membrane means within the cylindrical space compresses the membrane means and that the membrane means expands to its original form, when the compressing force of the plunger is released.
In a preferred embodiment of the invention the movement of the plunger moving in the cylindrical space of the end part of the suction device can be continued past the positions used for taking a sample or removing it, whereby the plunger or a telescopic extension thereof can be brought into contact with the membrane means, preferably with the membrane frame, or with pegs, shoulders, or other similar means belonging to the membrane means for releasing the membrane means from the end part of the suction device.
According to the invention the plunger moving within the cylindrical space of the end part of the suction device can move out of the end part through the opening in the distal end of the end part. The said plunger can also be provided with means such as shoulders, projections, pegs, fins, or other corresponding means, which can be brought into contact with the membrane means, preferably with the membrane frame, for releasing the membrane means from the end part of the suction device, when the plunger moves to the membrane means releasing position. The plunger can also be provided with a telescopic extension which can be brought into contact with the membrane means, preferably with the membrane frame, for releasing the membrane means from the end part of the suction device.
In a preferred embodiment of the invention, the membrane means can also comprise means, which, when releasing the membrane means with the movement of the plunger, can be brought into contact with the inner surface of the sample space of the tip removably mounted on the distal end of the end part of the suction device, or with means protruding from the inner surface into the sample space to bring about the removal of the tip from the end part of the suction device together with the removal of the membrane means.
According to an preferred embodiment of the invention, the membrane means can be removed from the end part of the suction device with tip removal means in the suction device e.g. when the membrane means is attached onto the end part of the suction device. In another preferred embodiment of the invention, the tip can be removed together with the membrane means with the removal means in the suction device.
The suction device according to the invention is also suitable for laboratory work based on the PCR-techniques, because the membrane means according to the invention prevents the DNA- and RNase-contamination of the inner parts of the pipette and thus the cross-contamination of different samples and reaction mixtures.
According to an alternative embodiment, used in an electronic pipette, the pipette is provided with identification means for identifying the membrane means alternative used and for communicating this information to a microprocessor of the pipette for bringing about a corresponding correction in the volumes dispensed by the pipette.
Further scope of the applicability of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.